| 重组碱性成纤维细胞生长因子通过Notch1信号通路对糖尿病大鼠视网膜神经节细胞的保护作用 |
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| 引用本文： | 王英,吴会平,王冬冬,刘学政.重组碱性成纤维细胞生长因子通过Notch1信号通路对糖尿病大鼠视网膜神经节细胞的保护作用[J].眼科新进展,2019,0(10):911-915. |
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| 作者姓名： | 王英 吴会平 王冬冬 刘学政 |
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| 作者单位： | 121001 辽宁省锦州市，锦州医科大学解剖学教研究(王英，刘学政)；121001 辽宁省锦州市，锦州医科大学附属第一医院(吴会平，王冬冬) |
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| 基金项目： | 国家自然科学基金资助(编号:81571383)~~ |
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| 摘 要： | 目的探讨重组碱性成纤维细胞生长因子(recombinant basic fibroblast growth factor,rbFGF)通过Notch1信号通路对糖尿病大鼠视网膜神经节细胞(retinal ganglion cell,RGC)的保护作用。方法雄性SD大鼠40只,随机分成对照组、糖尿病组、rbFGF组、rbFGF+DAPT组(DAPT为Notch1通路的特异性拮抗剂),每组10只。后三组大鼠采用单次腹腔注射链脲佐菌素(streptozotocin,STZ)诱导糖尿病模型。模型诱导成功后,rbFGF组给予rbFGF 10μL(200 U)玻璃体内注射给药,rbFGF+DAPT组在给予rbFGF基础上加用DAPT(10μmol·L^-1)。注射12周后,HE染色检测RGC密度,免疫组织化学染色检测神经元再生相关蛋白GAP-43、Notch1蛋白表达,Western blot检测GAP-43、Notch1蛋白及凋亡相关蛋白Caspase-3相对表达量。结果与对照组RGC密度(433.49±6.02)个·mm^-2,GAP-43荧光强度(8.96±0.26)%、Notch1阳性率(45.04±0.46)%及Caspase-3(27.91±0.63)%蛋白表达相比,糖尿病组RGC密度(328.35±6.43)mm^-2,Notch1荧光强度(31.66±0.40)%蛋白表达明显降低,GAP-43荧光强度(13.66±0.52)%、Caspase-3(48.91±0.64)%蛋白表达明显增加(均为P<0.05);而与糖尿病组相比,rbFGF组RGC密度(425.30±7.98)个·mm^-2,Notch1阳性率(41.76±0.62)%及GAP-43荧光强度(33.05±0.37)%蛋白表达明显增加,Caspase-3(28.86±0.71)%蛋白表达明显降低(均为P<0.05);而rbFGF+DAPT组RGC密度(324.91±8.22)个·mm^-2,GAP-43荧光强度(14.27±0.64)%、Notch1阳性率(30.40±0.82)%及Caspase-3(47.63±0.68)%蛋白表达均无明显变化(均为P>0.05)。结论rbFGF可上调糖尿病状态下视网膜GAP-43蛋白表达,下调Caspase-3蛋白表达,进而提高RGC的存活,其机制可能与激活Notch1信号通路有关。
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| 关 键 词： | 糖尿病视网膜病变 视网膜神经节细胞 重组碱性成纤维细胞生长因子 Notch1信号通路 生长相关蛋白-43 |
Protective effect of recombinant basic fibroblast growth factor on retinal ganglion cells via Notch1 signaling pathway in diabetic rats |
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| WANG Ying,WU Hui-Ping,WANG Dong-Dong,LIU Xue-Zheng.Protective effect of recombinant basic fibroblast growth factor on retinal ganglion cells via Notch1 signaling pathway in diabetic rats[J].Recent Advances in Ophthalmology,2019,0(10):911-915. |
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| Authors: | WANG Ying WU Hui-Ping WANG Dong-Dong LIU Xue-Zheng |
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| Affiliation: | Department of Anatomy,Jinzhou Medical University (WANG Ying,LIU Xue-Zheng),the First Affiliated Hospital of Jinzhou Medical University (WU Hui-Ping,WANG Dong-Dong),Jinzhou 121001,Liaoning Province,China |
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| Abstract: | Objective To investigate the protective effect of recombinant basic fibroblast growth factor (rbFGF) on retinal ganglion cell (RGC) in diabetic rats via Notch1 signaling pathway.Methods Totally 40 male SD rats were randomly divided into control group,diabetic group,rbFGF group,rbFGF+DAPT group (DAPT is a specific antagonist of Notch1 pathway),10 rats in each group.The diabetic rats in the latter three groups were induced by single intraperitoneal (IP) injection of streptozotocin (STZ).After successful induction of the model,rbFGF group was given intravitreal injection of rbFGF 10 μL (200 U),while rbFGF+DAPT group was given rbFGF 10 μL and DAPT (10 μmol·L-1).After 12 weeks of injection,the density of RGC was detected by HE staining,the protein expression of growth associated protein-43(GAP-43) and Notch1 was detected by immunohistochemical staining,and relative protein expression of GAP-43,Notch1 and Caspase-3 was detected by Western blot.Results Compared with the density of RGC ［(433.49±6.02)cells·mm-2］ and fluorescence intensity of GAP-43 ［(8.96±0.26)%］,positive rate of Notch1 ［(45.04±0.46)%］,the protein expression of Caspase-3［(27.91±0.63)%］ in the control group,the density of RGC ［(328.35±6.43)cells·mm-2］ and fluorescence intensity of Notch1 ［(31.66±0.40)%］ were decreased significantly,while the fluorescence intensity of GAP-43 ［(13.66±0.52)%］,the protein expression of Caspase-3 ［(48.91±0.64)%］ in diabetic group were increased significantly (all P<0.05).Compared with the diabetic group,the density of RGC ［(425.30±7.98)cells·mm-2］ and the fluorescence intensity of GAP-43 ［(33.05±0.37)%］,positive rate of Notch1［(41.76±0.62)%］ were increased significantly,while the protein expression of Caspase-3 ［(28.86±0.71)%］ in rbFGF group was decreased significantly (all P<0.05);but the density of RGC ［(324.91±8.22)cells·mm-2］,the fluorescence intensity of GAP-43 ［(14.27±0.64)%］,positive rate of Notch1［(30.40±0.82)%］ and the protein expression of Caspase-3［(47.63±0.68)%］ in rbFGF+DAPT group were no significantly change (all P>0.05).Conclusion RbFGF can up-regulate the protein expression of GAP-43 and down-regulate the protein expression of Caspase-3 in the retina of diabetes rats,thus improving the survival of RGC.The mechanism may be related to activation of Notch1 signaling pathway. |
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| Keywords: | diabetic retinopathy retinal ganglion cell recombinant basic fibroblast growth factor Notch1 signal pathway growth associated protein-43 |
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